Dataset Information

?-catenin mediates stress resilience through Dicer1/microRNA regulation.

ABSTRACT: ?-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice ?-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide ?-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis--as a ?-catenin target gene that mediates resilience. Small RNA profiling after excising ?-catenin from nucleus accumbens in the context of chronic stress reveals ?-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish ?-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.

SUBMITTER: Dias C

PROVIDER: S-EPMC4257892 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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β-catenin mediates stress resilience through Dicer1/microRNA regulation.

Dias Caroline C Feng Jian J Sun Haosheng H Shao Ning Yi NY Mazei-Robison Michelle S MS Damez-Werno Diane D Scobie Kimberly K Bagot Rosemary R LaBonté Benoit B Ribeiro Efrain E Liu XiaoChuan X Kennedy Pamela P Vialou Vincent V Ferguson Deveroux D Peña Catherine C Calipari Erin S ES Koo Ja Wook JW Mouzon Ezekiell E Ghose Subroto S Tamminga Carol C Neve Rachael R Shen Li L Nestler Eric J EJ

Nature 20141112 7529

β-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice β-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide β-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRN ...[more]

PMID: 25383518

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Project description:BackgroundCigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.MethodsThe present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT.ResultsBased on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling.ConclusionsIn summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

Dataset Information

?-catenin mediates stress resilience through Dicer1/microRNA regulation.

Publications

β-catenin mediates stress resilience through Dicer1/microRNA regulation.

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